Bronchioloalveolar Pattern Research Articles

A case of synchronous bilateral lung cancers: EML4-ALK positive adenocarcinoma in the right lung and adenocarcinoma in situ (the former bronchioloalveolar carcinoma) in the left lung

BackgroundRecently it has been revealed that lung adenocarcinomas with distinct gene mutations or fusions are associated with particular histopathological entities. For example, epidermal growth factor receptor (EGFR) gene mutations are often associated with well differentiated adenocarcinoma of the lung with bronchioloalveolar pattern. On the other hand, echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene in a subset of lung adenocarcinoma is related to mucinous cribriform histology.Case presentationReported herein is a case of synchronous EML4-ALK positive lung adenocarcinoma and adenocarcinoma in situ in the bilateral lungs of a 55-year-old Japanese woman. The woman had EML4-ALK positive lung adenocarcinoma in the right lower lung while adenocarcinoma in situ in the left upper lung, which was EML4-ALK negative.ConclusionTo our knowledge, this is the first report of synchronous, bilateral lung adenocarcinomas composed of EML4-ALK positive and negative ones.

INTERPHASE CYTOGENETIC ANALYSIS OF LUNG ADENOCARCINOMAS WITH BRONCHIOLOALVEOLAR PATTERN

Aneuploidy has been suggested as a marker for stratification of many neoplasms but its potential usefulness in adenocarcinoma (ADC) with bronchioloalveolar (BAC) pattern has not been well defined. We examined paraffin-embedded tissue sections from 28 cases of ADC with BAC pattern as well as 7 benign lung lesions and 9 normal lung tissue samples for chromosomal aneuploidy by in situ hybridization using digoxigenin-labelled probes for chromosomes 1 and X. Of the 28 ADC with BAC pattern, 17 (61%) were diploid and 11 (39%) were aneuploid. Of the 17 diploid cases, 7 (41%) were male and 10 (59%) were female and of the 11 aneuploid cases, 2 (18%) were male, 9 (82%) were female. Regarding the cell type, 24 (86%) were adenocarcinomas in situ (AIS) so called BAC and minimally invasive ADC (MIA), and 4 cases (14%) were invasive ADC. Of the 12 cases each of AIS and MIA, 9 (75%) and 8 (67%) had diploid pattern respectively. Of the 4 invasive ADC cases, all had aneuploid pattern. Seventeen cases (71%) with T1 tumor size (> 0 mm ≤30 mm), had diploid and 4 cases (100%) with T2 tumor size (> 30 mm ≤70 mm) had aneuploid pattern. Statistical analyses showed that nuclear diploidy was significantly correlated with AIS and MIA tumor types while aneuploidy correlated with invasive ADC type (P=0.025). Also a significant correlation was found between ploidy and tumor size (P=0.033). In conclusion, these findings suggest that DNA ploidy analysis provides useful information for the assessment of cellular kinetics and reflect histopathological subtypes in ADC with BAC pattern that are destined to behave aggressively.

Re: Bronchiolo-alveolar lung cancer: occurrence, surgical treatment and survival☆

Furak et al. [1] provide interesting data on bronchioloalveolar (BAC) lung cancer: occurrence, surgical treatment and survival; however, their pathological classification [2,3] as to what constitutes a BAC is not the current World Health Organization (WHO) definition [4]. Furak et al. defined BAC as an adenocarcinoma if more than 50% of the adenocarcinoma had a BAC component. The WHO classifies an adenocarcinoma with a BAC component as ‘adenocarcinoma mixed type with predominant bronchioloalveolar pattern’, regardless of the percentage of the BAC component. Most tumours described as BAC in the past would now be in this category. The present definition of BAC is much morerestrictive thananypreviouslyusedbymanypathologists.

Surgical Treatment of Multiple Primary Adenocarcinomas of the Lung

The incidence of lung adenocarcinomas has steadily increased over the last decades. The aim of this study was to assess the results of surgical treatment of multiple primary adenocarcinomas of the lung (MPAL) analyzing the radiological and histological features. From 1988 to 2005, 26 patients underwent surgical treatment for MPAL at our department, for a total of 52 tumors. Three patients had synchronous and 23 had metachronous tumors. Thirty-seven tumors were classified as solid, two as ground-glass opacities (GGO) and 13 as mixed solid/GGO tumors on the basis of CT scan evaluation. Histology revealed 26 adenocarcinomas, five adenocarcinomas with a bronchioloalveolar (BAC) pattern and 21 BAC. There was no postoperative mortality. Five-year survival of patients with synchronous tumors was 66 %. Survival of patients with metachronous tumors was 95 % and 70 % from the first and second operation. Patients with stage II and III a tumors had significantly reduced survival rates ( P < 0.05). Survival was 60 % after lobectomy and 78 % after wedge resection. Surgical treatment of MPAL is associated with favorable results. Sublobar resections, when technically feasible, provide adequate oncological management.

Pulmonary adenocarcinomas: classification and reporting

Pulmonary adenocarcinoma is the most common, and the most diverse form of primary lung carcinoma. The histological complexity of these tumours poses problems for pathologists. The current WHO classification of pulmonary adenocarcinoma does not adequately address a number of clinically relevant, biological factors. The accurate diagnosis of adenocarcinoma on small biopsy specimens, accounting for most diagnoses of this disease, is challenged by the absence of tumour architecture in most samples. Tumours showing a pure bronchioloalveolar (BAC) pattern are now best regarded as adenocarcinoma-in-situ; yet invasive adenocarcinomas may also show elements with the BAC pattern, dictating a better prognosis but biologically not necessarily in-situ disease. Multifocal BAC-pattern adenocarcinoma still poses considerable conceptual and diagnostic problems. In small tumours the papillary pattern, especially when micropapillary, confers a poor prognosis but this is not reflected in larger tumours. In early tumours of predominantly BAC (in-situ) pattern, the identification of invasion is particularly difficult, yet minor degrees of infiltration seem not to degrade prognosis. It may therefore be possible to define a minimally invasive category of adenocarcinoma. Consequently, there are a number of issues to consider when reporting this tumour type, depending on the nature of the diagnostic specimen. The rapid emergence of chemotherapeutic agents with histology-specific efficacy will increase the need for more accurate and specific diagnosis of adenocarcinoma on small samples. Immunohistochemistry may help suggest this diagnosis when the features are non-specific but immunohistochemical findings are not diagnostic of this form of lung cancer. The emerging clinical and prognostic relevance of a number of histological features in these complex tumours strengthens the argument in favour of including quantitative detail of pattern sub-types in reports on resected tumours.

Current issues in pulmonary adenocarcinoma

Pulmonary adenocarcinoma is the most prevalent and histologically diverse subtype of lung cancer, many aspects of which pose considerable clinical problems. A putative pathway of peripheral pulmonary adenocarcinogenesis is now established, as are criteria for distinguishing the initial lesion, atypical adenomatous hyperplasia, from the next, localized non-mucinous bronchioloalveolar carcinoma (LNMBAC), effectively adenocarcinoma-in-situ. The appearance of stromal invasion, with neofibroplasia, within LNMBAC defines adenocarcinoma, but alveolar collapse, which often precedes invasion, is an important differential diagnosis. The extent and location of invasion and neofibroplasia in early adenocarcinoma appears to be important. Adenocarcinomas show a diverse range of patterns. The bronchioloalveolar pattern may herald earlier disease and a better prognosis; papillary and solid patterns, more advanced disease. Mucinous tumours are biologically and histologically variable and pose particular diagnostic problems. Bronchioloalveolar carcinoma currently describes several biologically different lesions; a confusing situation, particularly when, in some contexts, this may indicate likely sensitivity to certain chemotherapeutic agents.

Diverse histologic appearances in pulmonary mucinous cystic neoplasia: A case report

IntroductionPrimary pulmonary mucinous cystic neoplasia comprises a group of tumors, from benign cystadenoma to mucinous cystadenocarcinoma.Case presentationWe report a case of primary pulmonary mucinous cystadenocarcinoma in a 75-year-old woman who was found to have a right hilar mass on a routine chest X-ray. A lobectomy was performed and the resection specimen revealed a multicystic mucinous tumor. Microscopically, the tumor was composed of confluent mucin-filled cystic spaces lined by columnar mucin-secreting cells which ranged from cytologically bland to moderately atypical with 'bronchioloalveolar pattern' invasion into the adjacent parenchyma. Immunohistochemically, tumor cells were positive diffusely for Cytokeratin 7, and focally for Cytokeratin 20 and Thyroid Transcription Factor-1.ConclusionThis case highlights the continuous spectrum of pulmonary mucinous cystic neoplasia from benign mucinous cystadenoma to malignant mucinous cystadenocarcinoma, and the probable existence of a 'borderline' mucinous cystic tumor. Although molecular data are lacking to substantiate progression from benign to malignant in these neoplasms, the importance of recognizing the morphologic continuum lies in alerting pathologists to thoroughly examine specimens to rule out invasive foci in tumors with 'borderline' morphology.

WWOX Expression in Different Histologic Types and Subtypes of Non–Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) has heterogeneous histopathologic classification and clinical behavior and very low survival rate. WWOX (WW domain-containing oxidoreductase) is a tumor suppressor gene, and its expression is altered in several cancers. The purpose of this study is to better define the role of WWOX in NSCLC tumorigenesis and progression by determining its pathogenetic and prognostic significance. WWOX protein expression was evaluated by immunohistochemistry in 170 patients with NSCLC (101 squamous cell carcinomas, 66 adenocarcinomas, 3 large cell carcinomas) and was correlated with histopathologic (histotype, subtype, grade, tumor-node-metastasis, stage, index of cell proliferation Ki67/MIB1) and clinical (age, gender, local recurrences, distant metastases, overall survival, and disease-free survival) characteristics. WWOX expression was absent/reduced in 84.9% of NSCLCs, whereas it was normal in 80.5% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology (P=1.1x10(-5)) and histologic grade (P=0.0081): the percentage of cases with absent/strongly reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated tumors. Regarding adenocarcinoma, bronchioloalveolar pattern showed normal WWOX expression in 62.5% of the cases, whereas in solid and acinar patterns, a prevalence of cases with absent/very low WWOX expression was observed (79.2% and 50%, respectively). Finally, weak WWOX staining intensity was related to the high index of cell proliferation (P=0.0012). Our results suggest that the loss of WWOX expression plays different roles in tumorigenesis of distinct histotypes and subtypes of NSCLC and is related to high aggressiveness (G3; high proliferating activity) of tumors.

Extent of bronchioloalveolar pattern and expression of the epidermal growth factor receptor in surgically resected lung adenocarcinomas

20065 Background: An increasing number of studies are exploring relations between the bronchioloalveolar differentiation of adenocarcinomas and clinical, radiological and molecular parameters. We investigated the potential relation between the extent of the bronchioloalveolar carcinoma (BAC) component of adenocarcinomas and the expression of the epidermal growth factor receptor (EGFR) protein. Methods: We retrospectively reviewed data from all patients who underwent surgery for lung cancer in our hospital between February 1, 2001 and May 31, 2005 (n = 366), and in whom pathologic analysis had revealed an adenocarcinoma histologic subtype. Paraffin embedded tissue samples were retrieved and re-examined. Samples exhibiting either a pure BAC histology or a mixed adenocarcinoma histology with a &gt;50% BAC component (n = 46) were selected for EGFR expression analysis by immunohistochemical staining. Patient demographics, stage and tumor differentiation data were recorded. Histological analysis was carried out using the WHO 1999/2004 criteria for lung cancers. For EGFR expression evaluation, samples were assigned a score ranging from 0 to +3. Expression was considered positive when the score was +1 or higher. Statistical analysis was performed using the chi-square test. Results: Of the 46 tumor samples examined, 10 had a BAC component of 50–79% (group A), 18 had BAC component of 80–99% (group B) and 18 exhibited a pure BAC histology (group C). Male/female ratio was 61.3%/38.7%. Mean age at presentation was 61.6 years. Among group A, 4 patients were EGFR positive and 6 were EGFR negative. 16 group B patients were EGFR positive and 2 were EGFR negative. Similarly, 16 group C patients were EGFR positive and 2 were EGFR negative. This distribution suggests that EGFR is more often expressed with increasing BAC component (p = 0.0041). No correlation was observed between demographics and EGFR expression or the extent of BAC pattern. Conclusions: EGFR expression is related to the extent of the BAC component in adenocarcinomas, with statistical significance. Study of a larger number of patients and correlation of this finding with EGFR and Ras mutational status and responsiveness to therapy are warranted. No significant financial relationships to disclose.

Synchronous Pulmonary Carcinoma and Pleural Diffuse Malignant Mesothelioma

Synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma is rare. Cases from the archives of 2 large referral centers were reviewed to identify cases of synchronously occurring pulmonary carcinoma and pleural diffuse malignant mesothelioma. Three cases of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma were identified from more than 16,000 pleuropulmonary cases and were reviewed for demographic, clinical, radiographic, histologic, and immunohistochemical findings. The patients were men who were 63, 67, and 77 years old. Two had positive smoking histories; the smoking history of the other patient is unknown. One patient had a positive history of asbestos exposure; one patient had no history of asbestos exposure; and one patient's history of asbestos exposure is unknown. The patients underwent surgery for treatment of adenocarcinoma that was diagnosed preoperatively. Two of the adenocarcinomas were of a predominantly bronchioloalveolar pattern. No diffuse malignant mesothelioma was identified preoperatively. Diffuse malignant mesothelioma was suspected on the basis of pleural involvement by tumor with histology differing from that of the adenocarcinoma. Tumor immunostaining supported the diagnoses. The average survival after diagnosis was 6 weeks or less. In summary, the paucity of cases at 2 large referral centers and the paucity of cases reported in the English language literature highlights the rarity of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma. These synchronous neoplasms occur in patients who have risk factors for both neoplasms independently. Length of survival following diagnosis is bleak.

Synchronous Pulmonary Carcinoma and Pleural Diffuse Malignant Mesothelioma

Synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma is rare. Cases from the archives of 2 large referral centers were reviewed to identify cases of synchronously occurring pulmonary carcinoma and pleural diffuse malignant mesothelioma. Three cases of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma were identified from more than 16,000 pleuropulmonary cases and were reviewed for demographic, clinical, radiographic, histologic, and immunohistochemical findings. The patients were men who were 63, 67, and 77 years old. Two had positive smoking histories; the smoking history of the other patient is unknown. One patient had a positive history of asbestos exposure; one patient had no history of asbestos exposure; and one patient's history of asbestos exposure is unknown. The patients underwent surgery for treatment of adenocarcinoma that was diagnosed preoperatively. Two of the adenocarcinomas were of a predominantly bronchioloalveolar pattern. No diffuse malignant mesothelioma was identified preoperatively. Diffuse malignant mesothelioma was suspected on the basis of pleural involvement by tumor with histology differing from that of the adenocarcinoma. Tumor immunostaining supported the diagnoses. The average survival after diagnosis was 6 weeks or less. In summary, the paucity of cases at 2 large referral centers and the paucity of cases reported in the English language literature highlights the rarity of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma. These synchronous neoplasms occur in patients who have risk factors for both neoplasms independently. Length of survival following diagnosis is bleak.

Surfactant Protein A Detection in Primary Pulmonary Adenocarcinoma without Bronchioloalveolar Pattern

Background: Immunohistochemical studies in human lung carcinoma reported positive staining of tumor cells for surfactant protein A (SP-A), especially in peripheral airway cell carcinoma, which include bronchioloalveolar carcinoma and in some reports also papillary subtypes. Objective: The purpose of this study was to determine the SP-A expression in tumor cells of lung adenocarcinoma without a bronchioloalveolar pattern, classified according to the WHO. Methods: In total, 169 primary adenocarcinomas of the lung (109 acinar, 32 solid with mucin, 24 papillary and 4 mucinous) were examined by immunohistochemistry for SP-A expression. Results: Twenty-five percent of acinar, 38% of papillary and 3% of solid adenocarcinoma with mucin showed a positive intracytoplasmic SP-A reaction of the tumor cells. None of the mucinous adenocarcinomas stained for SP-A. This study included the largest number of acinar adenocarcinomas and solid adenocarcinomas with mucin studied for SP-A. We clearly demonstrated that also primary lung adenocarcinoma without a bronchioloalveolar pattern can express SP-A. A positive staining of hyperplastic type II cells surrounding the tumors or entrapped in the tumor could clearly be differentiated from the SP-A-positive stain of tumor cells. Conclusion: These results support the theory that SP-A-producing cells may generate not only bronchioloalveolar and papillary carcinoma, but also other subtypes of lung adenocarcinoma.

Solitary metastatic renal cell carcinoma mimicking pulmonary adenocarcinoma with a bronchioloalveolar pattern: Radiologic–pathologic correlation

We present the high-resolution CT findings of solitary pulmonary metastasis resulting from a mixture of histologically different types of renal cell carcinoma that was difficult to distinguish from pulmonary adenocarcinoma with a bronchioloalveolar pattern in a 78-year-old man underwent a left nephrectomy for renal cell carcinoma

Surgical Treatments for Multiple Primary Adenocarcinoma of the Lung

Background The aim of this study was to identify the clinical characteristics of multiple primary adenocarcinomas and to evaluate the efficacy of surgical treatments. Methods Three-hundred sixty-nine patients who underwent pulmonary resection for adenocarcinoma from January 1994 to December 2002 were reviewed. Results Thirty-one patients (8.4%) were determined to have multiple primary adenocarcinomas that could be detected on chest x-rays or computed tomography (CT). Twenty-six patients were synchronous and five patients were metachronous with a median interval of 59.0 months. Forty-nine (72.1%) of the total 68 lesions exhibited ground-glass opacity on high-resolution CT (HRCT). Pathologically well-differentiated adenocarcinoma with mixed bronchioloalveolar pattern was the most common subtype (39.7%). Taking into consideration pulmonary function, size, location, and HRCT findings of the lesions the procedures performed were lobectomy with mediastinal lymph-node dissection for 32 patients, segmentectomy with hilar node dissection for 8 patients, and wedge resection for 28 patients. Of 17 patients with bilateral synchronous cancers, simultaneous bilateral pulmonary resection was performed in 14 patients including simultaneous bilateral video-assisted thoracic surgery (VATS) in 11 patients. After a median follow-up period of 27.7 months, the 3-year overall survival rate was 92.9% and the 3-year disease-free survival rates of synchronous cancer and metachronous cancer were 77.9% and 100%, respectively. Conclusions The incidence of multiple primary adenocarcinomas was relatively common. Early radiographic detection and surgical excision could yield a favorable prognosis. The use of VATS, even for synchronous bilateral patients, was a safe and beneficial procedure.

Cytopathologic Diagnosis of Bronchioloalveolar Carcinoma

We identified 29 bronchial washing, bronchoalveolar lavage, sputum, and fine-needle aspiration specimens with corresponding surgical pathology specimens with features of bronchioloalveolar carcinoma (BAC). Surgical pathology correlates were reclassified according to the 1999 World Health Organization classification into pure BAC, mixed adenocarcinoma–BAC (AD-BAC), and papillary adenocarcinoma (PAP-AD). Twelve cases of invasive pulmonary adenocarcinoma (INV-AD) without a bronchioloalveolar component were reviewed for comparison. The cytology slides were evaluated for 12 features of BAC. No statistically significant feature permitted separation of BAC from AD-BAC or from PAP-AD. However, comparison of BAC with INV-AD identified 9 statistically significant cytologic features: clean background, absence of 3-dimensional clusters, neoplastic cells in flat sheets, orderly arrangement of cells with round uniform nuclei, predominance of mucinous cells, absence of nuclear overlap, absence of irregular nuclear membranes, fine granular chromatin, and nuclear grooves that were features of BAC cases. Although cytologic evaluation cannot prospectively diagnose BAC, the bronchioloalveolar pattern may be recognized and suggests in situ proliferation that is present in BAC, AD-BAC, or PAP-AD. The bronchioloalveolar pattern must be correlated with clinical, radiographic, and histologic parameters to determine whether the tumor is localized, multifocal, or diffuse and whether there is parenchymal invasion.

Patterns of recurrence of bronchioloalveolar cell carcinoma after surgical resection: a radiological, histological, and immunohistochemical study

Purpose: Bronchioloalveolar carcinoma (BAC) is a subtype of lung adenocarcinoma whose incidence is raising. Bronchioloalveolar carcinoma has a tendency to involve diffusely the lung. No agreement exists about whether diffuse bronchioloalveolar carcinoma has a multicentric or unicentric origin. The purpose of this work is to evaluate the correlation between intrapulmonary spread of bronchioloalveolar carcinoma and its histologic and immunohistochemical characteristics. Design: Surgical specimens of 20 bronchioloalveolar carcinomas with radiologically proved evolution from focal to diffuse disease were retrieved and reviewed. Patterns of pulmonary spread were defined on the basis of CT and MR imaging examinations. Immunohistochemical studies were performed to investigate the expression of gelatinase A and α2-integrin. Correlation between immunohistochemical results and patterns of pulmonary spread was evaluated. Statistical evaluation was performed by using Fisher Exact Test. Results: Three histological subtypes of bronchioloalveolar carcinoma were found: mucinous (11 cases), non-mucinous (3 cases), and mixed adenocarcinoma with prominent bronchioloalveolar pattern (6 cases). Three patterns of pulmonary spread were depicted radiologically: parenchymal opacification (11 cases), multiple nodules (7 cases) and mixed pattern (2 cases). Eleven out of 12 mucin-producing versus none out of 8 non-mucin producing cancers developed parenchymal opacification. The difference was statistically significant ( P<0.028). A statistically significant difference was also found between the development of parenchymal opacification and the level of α2-integrin: 11 out of 13 tumors with negative α2-integrin versus none out of 7 with positive α2-integrin immunoreactivity ( P>0.033). Conclusions: Diffuse bronchioloalveolar carcinoma may develop from a prior focal cancer. Mucinous subtype is the most prone to develop diffuse disease with parenchymal opacification, probably representing aerogenous spread. Low levels of α2-integrin receptors were found in bronchioloalveolar carcinoma which developed parenchymal opacification.

Prognostic significance of percentage of bronchioloalveolar pattern in adenocarcinomas of the lung.

Bronchioloalveolar (BA) carcinoma of the lung is considered to have a better prognosis than that of common adenocarcinomas of the lung. However, a minor component of the BA pattern is common in many lung adenocarcinomas and the criteria for designating an adenocarcinoma as BA are not well defined. We assessed the clinicopathologic features of 238 cases of lung adenocarcinoma with a partial or predominant BA pattern. Tumors were classified as BA if more than 75% of the tumor had a BA growth pattern. In other words, the tumor grew along pre-existing lung structures without invasion or destruction of parenchyma. Tumors with 50% to 75% BA pattern were considered mixed and tumors with less than 50% BA pattern were designated as solid/acinar (S/A). Fixed, paraffin-embedded tissue sections of each neoplasm were also assessed using immunohistochemical methods with a panel of antibodies specific for p53, retinoblastoma protein, p16, cyclin D1, and cyclin E, and the results were correlated with clinical and pathologic parameters. Our results show that the 5-year survival rate of patients with BA and mixed tumors, 63% and 60%, respectively, was significantly better than that of patients with S/A tumors (P =.026). Patients with BA tumors were more frequently women (55.9%) compared with patients with mixed (48.3%) and S/A (43.8%) tumors. Bronchioloalveolar and mixed tumors were similarly associated with tobacco use, 88.2% and 85%, respectively; slightly less than S/A tumors (93.8%). Clinical and pathologic parameters did not correlate with immunohistochemical results. In conclusion, patients with BA or mixed tumors have similar 5-year survival, better than that of patients with S/A tumors, suggesting that adenocarcinomas can be designated as BA when at least 50% of the tumor has a BA pattern.

Expression of CD44v6 but not E‐cadherin or β‐catenin influences prognosis in primary pulmonary adenocarcinoma

Primary pulmonary adenocarcinoma was studied, looking for relationships between the expression of cell adhesion molecules (CAMs) E-cadherin, β-catenin and CD44v6, and clinicopathological tumour parameters and patient post-operative survival. Formalin-fixed, paraffin-embedded tissue from 120 primary lung adenocarcinomas, including 23 poorly differentiated tumours, 17 of probable bronchial origin, and 29 with a prominent bronchioloalveolar pattern, together with nodal metastatic tumour from 34 of these patients was stained using monoclonal antibodies and immunohistochemistry. Sections were scored either high level (>10% cells positive) or low level (<10% positive). High level expression of CD44v6 was retained in 28.4% (34/120) of tumours, while high levels of E-cadherin (57.5%, 69/120) and β-catenin (80.8%, 97/120) were more frequent. For all CAMs, staining levels did not correlate with nodal status, stage or tumour type. The apical or basal staining seen in normal bronchial and alveolar epithelium was often seen in papillary, glandular, and bronchioloalveolar areas of tumour, while solid invasive tumour more often showed pericellular staining. When the staining for each CAM in 34 nodal metastases was compared with that in the corresponding primary tumour, a high degree of concordance was found, with no tendency for metastases to show less staining than the primary tumour. Expression of E-cadherin and β-catenin in the primary tumour had no influence on post-operative survival, but patients whose tumours had low level CD44v6 expression had a poorer post-operative survival than those with high levels of CD44v6 (p=0.0014 for all patients, p=0.0012 for stage I patients only). In primary pulmonary adenocarcinoma, the levels of expression of E-cadherin, β-catenin, and CD44v6 are not associated with lymph node metastases or tumour stage but the staining pattern is associated with tumour morphology. Low levels of CD44v6 expression predict a poor post-operative survival, independently of stage, while there is no such relationship with the expression of E-cadherin or β-catenin. Copyright © 2000 John Wiley & Sons, Ltd.

Expression of CD44v6 but not E-cadherin or beta-catenin influences prognosis in primary pulmonary adenocarcinoma.

Primary pulmonary adenocarcinoma was studied, looking for relationships between the expression of cell adhesion molecules (CAMs) E-cadherin, beta-catenin and CD44v6, and clinicopathological tumour parameters and patient post-operative survival. Formalin-fixed, paraffin-embedded tissue from 120 primary lung adenocarcinomas, including 23 poorly differentiated tumours, 17 of probable bronchial origin, and 29 with a prominent bronchioloalveolar pattern, together with nodal metastatic tumour from 34 of these patients was stained using monoclonal antibodies and immunohistochemistry. Sections were scored either high level (>10% cells positive) or low level (<10% positive). High level expression of CD44v6 was retained in 28.4% (34/120) of tumours, while high levels of E-cadherin (57.5%, 69/120) and beta-catenin (80. 8%, 97/120) were more frequent. For all CAMs, staining levels did not correlate with nodal status, stage or tumour type. The apical or basal staining seen in normal bronchial and alveolar epithelium was often seen in papillary, glandular, and bronchioloalveolar areas of tumour, while solid invasive tumour more often showed pericellular staining. When the staining for each CAM in 34 nodal metastases was compared with that in the corresponding primary tumour, a high degree of concordance was found, with no tendency for metastases to show less staining than the primary tumour. Expression of E-cadherin and beta-catenin in the primary tumour had no influence on post-operative survival, but patients whose tumours had low level CD44v6 expression had a poorer post-operative survival than those with high levels of CD44v6 (p=0.0014 for all patients, p=0.0012 for stage I patients only). In primary pulmonary adenocarcinoma, the levels of expression of E-cadherin, beta-catenin, and CD44v6 are not associated with lymph node metastases or tumour stage but the staining pattern is associated with tumour morphology. Low levels of CD44v6 expression predict a poor post-operative survival, independently of stage, while there is no such relationship with the expression of E-cadherin or beta-catenin.

Heterogeneity of Histiocytes in Primary Lung Cancer Stained with Anti-S100 Protein, Lysozyme and OKT 6 Antibodies

The heterogeneity of histiocytes in primary lung cancer was investigated by immunohistochemical methods using anti-S100 protein and anti-lysozyme antibodies on paraffin sections and OKT-6 monoclonal antibody on frozen sections. T-zone histiocytes (Langerhans cells and their precursors stained by anti-S100 protein and/or OKT-6 monoclonal antibodies) heavily infiltrated tumor tissues and regional lymph nodes in cases of moderately or well-differentiated adenocarcinoma, especially in areas of papillary growth or bronchiolo-alveolar pattern. These cells were interspersed amongst tumor cells showing dendritic figures and were occasionally present in squamous cell carcinoma. However, they were seldom found in other histological types, particularly in small cell carcinoma and carcinoid tumor. The distribution of these cells was different from that of lysozyme-positive macrophages. In this connection, T-zone histiocytes were thought to have a different immunological function from that of the monocyte-macrophage series against lung cancer. The closely similar reactivity of T-zone histiocytes with anti-S100 protein and OKT-6 monoclonal antibodies indicated that these two markers can be employed for paraffin and frozen sections, respectively.